Satavaptan

Ascites formation is a sign of decompensation of cirrhosis and heralds a poor prognosis. The widely used standard binary classification of ascites as diuretic‐responsive or refractory does not cover the spectrum of ascites and has limited prognostic information. We developed the Cirrhotic Ascites Severity (CIRAS) model to predict 1‐year mortality among 465 patients randomized to placebo in the satavaptan trials investigating treatment of cirrhotic ascites. We used multivariable logistic regression to derive the CIRAS model based on these variables: ascites discomfort score (≤50 or >50), plasma sodium (≥140, 133–139, 125–132, or <125 mmoL/L), and a composite of ascites accumulation and diuretic treatment. We validated the prediction model in 697 trial participants randomized to satavaptan treatment. The 1‐year all‐cause mortality was 19.6%. The area under the receiver operator curve was higher for the CIRAS model than for the standard ascites classification into refractory and diuretic‐responsive in both the development cohort (0.68 [95% confidence interval (CI): 0.62–0.75] vs. 0.62 [0.57–0.68]), and the validation cohort (0.68 [0.64–0.72] vs. 0.55 [0.51–0.60]). The CIRAS model had similar discrimination to the Child‐Pugh score and nearly as good as the Model for End‐Stage Liver Disease (MELD), MELD‐Na, and MELD 3.0. Conclusions: The CIRAS model based on simple ascites‐relevant data is an easily applicable and patient‐centered way to describe the severity and prognosis of all ascites grades. It carries more prognostic information than today's label of “refractory ascites” and forms the basis for earlier and better clinical decisions related to ascites management.

Spontaneous bacterial peritonitis (SBP) is a frequent complication to cirrhosis with an unclear long-term prognosis. We aimed to examine its effect on mortality in two independent patient cohorts.

We used Danish healthcare data on cirrhosis patients with a first-time paracentesis in 2000-2014 and data from three randomized controlled trials on satavaptan treatment of ascites conducted in 2006-2008. We used the Kaplan-Meier method to estimate cumulative mortality, and Cox regression to compare the confounder-adjusted mortality hazard for patients with vs. without SBP.

In the Danish Healthcare Cohort, we included 1.282 patients of whom 133 (10.4%) had SBP. The SBP patients' cumulative 4-month mortality was 51.2% (95% CI: 43.0-59.9%) vs. 34.7% (95% CI: 32.0-37.6) in those without SBP. The SBP patients' confounder-adjusted mortality hazard was 1.54-fold higher (95% CI: 1.18-2.00) in the four months after paracentesis, but was not increased thereafter (confounder-adjusted mortality hazard 1.02, 95% 0.72-1.46). In the satavaptan trial data of 1,198 cirrhosis patients with ascites, the 93 patients with SBP had a cumulative 4-month mortality of 38.6% (95% CI: 29.3-49.7) compared with 11.4% (95% CI: 8.5-15.2) in those without. The SBP patients' confounder-adjusted mortality hazard ratio was 3.86 (95% CI: 2.44-6.12) during the first four months, and was 1.23 (95% CI: 0.54-2.83) thereafter.

In both cohorts of patients with cirrhosis, an SBP episode had a high short-term mortality compared to patients without SBP, and had no lasting effect on the long-term mortality.